ABSTRACT Cryptococcosis and tuberculosis are the leading causes of death in patients with HIV/AIDS in sub-Saharan, including patients initiating antiretroviral therapy (ART). Although there are increasing efforts to facilitate early diagnosis of TB in patients initiating ART, there are only a few programs that have focused attention on the early diagnosis and treatment of cryptococcal disease to decrease cryptococcosis associated morbidity and mortality. Early diagnosis of cryptococcal disease can be achieved by effectively screening patients with low CD4 counts (<100cells/mm3) prior to the initiation of ART. The recent development of the lateral flow assay (LFA), a low cost point of care test that does not require expensive equipment or a highly skilled laboratory technician provides an opportunity for early diagnosis of cryptococcal disease in resource limited settings. We propose to evaluate the implementation of a screening program for cryptococcosis at a large public HIV/ART treatment centre in Harare, Zimbabwe. The primary objective is to decrease morbidity and mortality associated with the initiation of ART by decreasing morbidity and mortality due to cryptococcosis. We will test the performance of the LFA against gold standards (cryptococcal antigen latex agglutination assays, blood and CSF cultures) and determine its sensitivity and specificity in whole blood (finger stick) and urine. We also propose to develop a meningitis risk score that can be used by remote facilities to identify among patients with a positive LFA test which patients are at greatest risk of cryptococcal meningitis and require transfer to better resourced facilities for spinal taps and intravenous antifungal therapy. The successful implementation of this screening program through the use of low cost interventions has the potential to decrease incident cryptococcosis in ART treatment programs in sub-Saharan Africa.